PROJECT SUMMARY American Indians (AI) in Minnesota have 5-6x the opioid overdose death rate of other groups, and this figure continues to rise. Medication-assisted treatment (MAT) is the standard of care for opioid use disorder (OUD) treatment, but implementation and uptake has been slow nationally, especially for AI communities. Thus, there is an urgent need to understand multi-level barriers and facilitators of OUD treatment, including how AI cultural knowledge and practices can be interwoven within OUD treatment and how engagement can be improved along all points of the OUD ?Cascade of Care? (CoC). This project will involve a partnership between the University of Minnesota Medical School, Duluth Campus, and a rural Minnesota tribal Nation. The overall objective of this application is to characterize the OUD CoC in a reservation-based, tribal treatment context. Our central hypothesis is that AIs benefit from MAT programs and OUD treatment, but there are multi-level barriers and facilitators that affect implementation of the CoC, some unique to tribal communities. The rationale for this project is that careful assessment of factors influencing the OUD CoC with AIs will optimize treatment implementation and ultimately reduce opioid-related heath inequities. The preparatory R61 aims include (1) characterizing the OUD CoC in a tribal context and delineating its components and transition points using community-based participatory research (CBPR) methods and data from existing sources; (2) identifying barriers and facilitators to engagement with the OUD CoC at key transition points via interviews with clinical stakeholders and individuals with OUD and their families, and (3) preparing and confirming feasibility of observational longitudinal data collection (R33 Aim 1) by developing and piloting study protocols and measures. The R33 aims include: (1) prospectively examining barriers and facilitators to treatment engagement and clinical outcomes defined within the CoC among 200 AIs with OUD after initial MAT clinic intake assessment, and (2) identifying a set of culturally-centered, evidence-based implementation strategies to address barriers and optimize treatment engagement across the CoC. The proposed project will leverage and complement the tribe?s SAMHSA Tribal Opioid Response and MAT Prescription Drug and Opioid Addiction funding. It is innovative because it considers barriers and facilitators across the entire OUD CoC in a tribal context, and is one of the first studies to apply a dissemination and implementation lens to opioid research with AI communities. The expected outcomes of the research include a culturally-centered description of the OUD Cascade of Care with identified implementation strategies to address barriers to engagement. Findings would provide generalizable scientific knowledge to optimize OUD services to reduce opioid-related health inequities for American Indians.